DMMC Course: EPIGENETICS: FROM MECHANISMS TO MEDICINES

0810-0840 Tuesday 26 June 2007. O’Reilly Hall, University College Dublin.

An Introduction to DNA Methyltransferase Inhibitors
Dr Helen Gallagher (University College Dublin)

Unlike mutations in DNA sequence, epigenetic changes, such as promoter hypermethylation and epigenetic silencing of tumor suppressor genes, are considered reversible, in that they must be maintained for their effects on gene function to persist within an organism. As a consequence of this reversibility, epigenetic changes are promising drug targets for the treatments of various diseases, most notably cancer. Several agents, which reverse promoter methylation or inhibit histone deacetylases, are under development for use in a variety of neoplastic diseases and results from preliminary clinical trials are promising. In this lecture, we will introduce and discuss the mechanisms of action of DNA methyltransferase inhibitors. We also discuss future areas of pharmacological research in the regulation of methylation, including the need to define molecular endpoints so that changes induced in patients by demethylating drugs can be monitored during their treatment.